The CaV2.3 Ca2+ channel subunit contributes to R‐Type Ca2+ currents in murine hippocampal and neocortical neurones

Сочивко, Д. Г.; Pereverzev, Alexey; Smyth, Neil; Gissel, Cornelia; Schneider, Toni; Beck, Hanno

doi:10.1113/jphysiol.2002.020677

Cited by 81 publications

(74 citation statements)

References 56 publications

(104 reference statements)

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“…Considerable evidence now supports the view that native R-type Ca 2ϩ currents are conducted primarily through Ca V 2.3 channel subunits (Piedras-Rentería and Tsien, 1998;Tottene et al, 2000;Lee et al, 2002;Sochivko et al, 2002; but see Wilson et al, 2000). Ca V 2.3 is expressed in neurons (Niidome et al, 1992;Soong et al, 1993;Williams et al, 1994;Grabsch et al, 2000) and seems to be localized to somatic and dendritic membranes (Yokoyama et al, 1995;Day et al, 1996), suggesting the possible involvement of Ca V 2.3 in dendritic excitability (Delmas et al, 2000) or control of gene expression.…”

mentioning

confidence: 79%

Differential Modulation of Ca_V2.3 Ca²⁺Channels by Gαq/11-Coupled Muscarinic Receptors

Bannister

Melliti²,

Adams³

2004

Mol Pharmacol

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Ca V 2.3 subunits are expressed in neuronal and neuroendocrine cells where they are believed to form native R-type Ca 2ϩ channels. Although R-type currents are involved in triggering neurotransmitter and hormone secretion, little is known about their modulation. Previous studies have shown that muscarinic acetylcholine receptors evoke both inhibition and stimulation of Ca V 2.3. Muscarinic inhibition of Ca V 2.3 is mediated by G␤␥ subunits, whereas stimulation is mediated by pertussis toxininsensitive G␣ subunits. In the present study, we compared modulation of Ca V 2.3 by the three G␣q/11-coupled muscarinic receptors (M1, M3, and M5). Our data indicate that these receptors trigger comparable stimulation of Ca V 2.3. The signaling pathway that mediates stimulation was meticulously analyzed for M1 receptors. Stimulation is blocked by neutralizing antibodies directed against G␣q/11, coexpression of the regulatory domain of protein kinase C␦ (PKC␦), preactivating PKC with phorbol ester, or pharmacological suppression of PKC with bisindolylmaleimide I. Stimulation of Ca V 2.3 is Ca 2ϩ -independent and insensitive to 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole (Gö 6976), a specific inhibitor of Ca 2ϩ -dependent PKC isozymes. These results indicate that muscarinic stimulation of Ca V 2.3 involves signaling by G␣q/11, diacylglycerol, and a Ca 2ϩ -independent PKC. In contrast to stimulation, the magnitude of Ca V 2.3 inhibition depended on receptor subtype, with M3 and M5 receptors producing much larger Ca V 2.3 inhibition than M1 receptors. Interestingly, muscarinic inhibition of Ca V 2.3 was notably enhanced during pharmacological suppression of PKC, suggesting the presence of cross-talk between G␤␥-mediated inhibition and PKC-mediated stimulation of R-type channels similar to that described previously for N-type channels.

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mentioning

confidence: 79%

Differential Modulation of Ca_V2.3 Ca²⁺Channels by Gαq/11-Coupled Muscarinic Receptors

Bannister

Melliti²,

Adams³

2004

Mol Pharmacol

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“…Although the ADP was not blocked by the Ca V 2.3 (␣ 1E ) blocker SNX-482, it remains possible that the current underlying the ADP is mediated by an SNX-resistant isoform of Ca V 2.3 (Tottene et al, 2000). In addition, mice lacking Ca V 2.3 subunits still contain blocker-resistant calcium current (Wilson et al, 2000;Lee et al, 2002;Sochivko et al, 2002), so other molecular components may contribute to R-type current.…”

Section: A Novel Role For R-type Calcium Currentmentioning

confidence: 99%

“…Both T-and R-type calcium currents are sensitive to Ni 2ϩ and resistant to selective antagonists (Bean, 1989;Tsien et al, 1991;Soong et al, 1993;Zhang et al, 1993;Eliot and Johnston, 1994;Tottene et al, 1996Tottene et al, , 2000Zamponi et al, 1996;Yu and Shinnick-Gallagher, 1997;Lee et al, 1999;Foehring et al, 2000;Sochivko et al, 2002Sochivko et al, , 2003; however, the majority of the blocker-resistant calcium current in CA1 pyramidal neurons has been attributed to R-type current (Sochivko et al, , 2003. In voltage clamp, the high halfactivation voltage and rapid deactivation of the calcium tail current are more consistent with R-type current than T-type current (Bean, 1989;Takahashi et al, 1991;Tsien, 1991;Tsien, 1995, 1997;Hilaire et al, 1997;Yu and Shinnick-Gallagher, 1997;Nakashima et al, 1998;PiedrasRenteria and Tsien, 1998;Foehring et al, 2000;Magistretti et al, 2000;Tottene et al, 2000;Wilson et al, 2000;Lee et al, 2002).…”

Section: R-type Versus T-type Calcium Currentmentioning

confidence: 99%

R-Type Calcium Channels Contribute to Afterdepolarization and Bursting in Hippocampal CA1 Pyramidal Neurons

Metz

Jarsky²,

Martina³

et al. 2005

Journal of Neuroscience

160

150

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Action potentials in pyramidal neurons are typically followed by an afterdepolarization (ADP), which in many cells contributes to intrinsic burst firing. Despite the ubiquity of this common excitable property, the responsible ion channels have not been identified. Using current-clamp recordings in hippocampal slices, we find that the ADP in CA1 pyramidal neurons is mediated by an Ni 2ϩ -sensitive calcium tail current. Voltage-clamp experiments indicate that the Ni 2ϩ -sensitive current has a pharmacological and biophysical profile consistent with R-type calcium channels. These channels are available at the resting potential, are activated by the action potential, and remain open long enough to drive the ADP. Because the ADP correlates directly with burst firing in CA1 neurons, R-type calcium channels are crucial to this important cellular behavior, which is known to encode hippocampal place fields and enhance synaptic plasticity.

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“…Interestingly, SNX-482, a selective antagonist of recombinant ␣ 1E channels, failed to block R-type Ca 2ϩ currents in MPG neurons, which is also observed in several types of central neurons including rat cerebellar granule neurons (Newcomb et al, 1998). Recent studies using antisense or transgenic strategies have shown that the ␣ 1E gives rise to SNX-482-sensitive and -resistant components (Piedras-Renteria and Tsien, 1998;Tottene et al, 2000;Sochivko et al, 2002), whose relative contribution to R-type Ca 2ϩ currents may vary from one cell to another cell. Like P/Q-type Ca 2ϩ currents as explained above (Moreno et al, 1997;Bourinet et al, 1999), R-type Ca 2ϩ currents showing different toxin sensitivity may also arise from alternative splicing and/or heterogeneity of Ca 2ϩ channel auxiliary subunits.…”

Section: ؉mentioning

confidence: 99%

“…Recently, another spider toxin called SNX-482 became available for selectively blocking R-type calcium channels (Newcomb et al, 1998). However, splicing variants of R-type Ca 2ϩ channels resistant to SNX-482 also have been described in some central nervous system neurons, such as retinal ganglion neurons, hippocampal CA1 neurons, and cerebellar granule neurons (Newcomb et al, 1998;Tottene et al, 2000;Sochivko et al, 2002).…”

mentioning

confidence: 99%

Expression Profiles of High Voltage-Activated Calcium Channels in Sympathetic and Parasympathetic Pelvic Ganglion Neurons Innervating the Urogenital System

Won

Whang

Kong

et al. 2006

J Pharmacol Exp Ther

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Among the autonomic ganglia, major pelvic ganglia (MPG) innervating the urogenital system are unique because both sympathetic and parasympathetic neurons are colocalized within one ganglion capsule. Sympathetic MPG neurons are discriminated from parasympathetic ones by expression of low voltage-activated Ca 2ϩ channels that primarily arise from T-type ␣ 1H isoform and contribute to the generation of low-threshold spikes. Until now, however, expression profiles of high voltageactivated (HVA) Ca 2ϩ channels in these two populations of MPG neurons remain unknown. Thus, in the present study, we dissected out HVA Ca 2ϩ channels using pharmacological and molecular biological tools. Reverse transcription-polymerase chain reaction analysis showed that MPG neurons contained transcripts encoding all of the known HVA Ca 2ϩ channel isoforms (␣ 1B , ␣ 1C , ␣ 1D , and ␣ 1E ), with the exception of ␣ 1A . Western blot analysis and pharmacology with -agatoxin IVA (1 M) confirmed that MPG neurons lack the ␣ 1A Ca 2ϩ channels. Unexpectedly, the expression profile of HVA Ca 2ϩ channel isoforms was identical in the sympathetic and parasympathetic neurons of the MPG. Of the total Ca 2ϩ currents, -conotoxin GVIA-sensitive N-type (␣ 1B ) currents constituted 57 Ϯ 5% (n ϭ 9) and 60 Ϯ 3% (n ϭ 6), respectively; nimodipine-sensitive L-type (␣ 1C and ␣ 1D ) currents made up 17 Ϯ 4% and 14 Ϯ 2%, respectively; and nimodipine-resistant and -conotoxin GVIAresistant R-type currents were 25 Ϯ 3% and 22 Ϯ 2%, respectively. The R-type Ca 2ϩ currents were sensitive to NiCl 2 (IC 50 ϭ 22 Ϯ 0.1 M) but not to SNX-482, which was able to potently (IC 50 ϭ 76 Ϯ 0.4 nM) block the recombinant ␣ 1E /␤ 2a /␣ 2 ␦ Ca 2ϩ currents expressed in human embryonic kidney 293 cells. Taken together, our data suggest that sympathetic and parasympathetic MPG neurons share a similar but unique profile of HVA Ca 2ϩ channel isoforms.

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The Ca_V2.3 Ca²⁺ channel subunit contributes to R‐Type Ca²⁺ currents in murine hippocampal and neocortical neurones

Cited by 81 publications

References 56 publications

Differential Modulation of Ca_V2.3 Ca²⁺Channels by Gαq/11-Coupled Muscarinic Receptors

Differential Modulation of Ca_V2.3 Ca²⁺Channels by Gαq/11-Coupled Muscarinic Receptors

R-Type Calcium Channels Contribute to Afterdepolarization and Bursting in Hippocampal CA1 Pyramidal Neurons

Expression Profiles of High Voltage-Activated Calcium Channels in Sympathetic and Parasympathetic Pelvic Ganglion Neurons Innervating the Urogenital System

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The CaV2.3 Ca2+ channel subunit contributes to R‐Type Ca2+ currents in murine hippocampal and neocortical neurones

Cited by 81 publications

References 56 publications

Differential Modulation of CaV2.3 Ca2+Channels by Gαq/11-Coupled Muscarinic Receptors

Differential Modulation of CaV2.3 Ca2+Channels by Gαq/11-Coupled Muscarinic Receptors

R-Type Calcium Channels Contribute to Afterdepolarization and Bursting in Hippocampal CA1 Pyramidal Neurons

Expression Profiles of High Voltage-Activated Calcium Channels in Sympathetic and Parasympathetic Pelvic Ganglion Neurons Innervating the Urogenital System

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The Ca_V2.3 Ca²⁺ channel subunit contributes to R‐Type Ca²⁺ currents in murine hippocampal and neocortical neurones

Differential Modulation of Ca_V2.3 Ca²⁺Channels by Gαq/11-Coupled Muscarinic Receptors

Differential Modulation of Ca_V2.3 Ca²⁺Channels by Gαq/11-Coupled Muscarinic Receptors